The mechanisms that underlie the orderly sequential changes in gene expression during neurogenesis are unknown, It is now clear that these communications regulate neuroblast development, axonal growth and guidance, and ultimately synapse formation, The molecular machinery that relays this information is the foundation upon which neuronal diversity and function is based. Over the past two years, we have searched for, identified and cloned three new genes involved in the neurogenesis of the fruit fly, Drosophila melanogaster. This past year, we have focused our efforts on characterization of these genes by studying their expression, generating multiple mutant alleles for each, and analyzing the consequences of their mutations. Recently, we have used a recombinant protein to generate polyclonal antibodies against one of the encoded proteins. We plan to use this information and these newly acquired tools to study nervous system development in Drosophila and ultimately search for functionally related genes in mammals. Homeodomain proteins represent a highly conserved family of regulatory factors that play an important role in establishing the body plan of metazoans. To understand the biologic function of homeodomain proteins, it is necessary to identify the genes whose expression is regulated by these transcription factors. To determine the in vivo biofunction of the murine Hox 1.3 homeodomain protein, i.e., identify genes that are regulated by this putative transcription factor, we are screening cDNA libraries constructed from transgenic mice that contain an inducible Hox 1.3 transgene with subtracted cDNA probes.